Materials that are used to fabricate articles that contact fluids, such as filters, biosensors, and implantable medical devices, are generally chosen for their bulk physical properties rather than for the properties these materials may confer to the article surface. As a result, while the object may have desirable properties such as strength and elasticity, its surface may not be optimized for interactions with fluids. Conventional methods and materials for the surface modification of such devices can be used, for instance, to decrease protein adsorption, increase wettability and lubricity, and decrease thrombus formation and bacterial colonization.
Conventional coating processes typically involve steps of preparing a coating composition that includes polymeric material, applying the compositions to the surface of a substrate, and then drying and curing the composition to form a polymeric coating on the surface of the substrate. In many coating procedures, coating compositions are applied to the surface by dip-coating or by spraying, and then are allowed to dry. However, these conventional coating techniques and reagents are frequently not well designed for applications that require very thin coatings. More typically these techniques result in coatings that are greater than 0.5 microns in thickness.
Various attempts have been made to provide passivated, biomolecule-compatible synthetic surfaces. These attempts have included the design and production of improved plastics, as well as the use of thin-film coatings of plastic, silica, semiconductor, and metal surfaces. Thin film coatings have tended to rely upon the adsorption and thermochemical bonding of preformed hydrophilic and surfactant polymers, in situ polymerization/crosslinking to form hydrophilic but insoluble polymeric films, or photochemical bonding of preformed hydrophilic and surfactant polymers after an article has been dip-coated in a coating solution.
Relatively thinner coatings can be prepared by vapor deposition polymerization (VDP). In VDP, monomer product is vaporized in a reaction chamber in the presence of a substrate. The vaporized monomer radical resublimates on the surface of the substrate, and reacts with other monomer radicals on the surface to form a thin polymer layer. Parylene™ (poly(para-xylylene)) coatings are commonly formed by VDP processes. Although these coatings are relatively very thin, they typically do not have thicknesses of less than 100 nm. Typically, poly(para-xylylene) coated layers are in the range of about 0.1 micron to about 75 microns in thickness. Even these relatively thin coatings that are formed by plasma deposition processes have the potential to provide coatings that may be too thick for some applications.
More recently, the preparation of “ultra-thin” coatings has been achieved. As referred to herein, “ultra thin” coatings can be considered to have a thickness of about 20 nm or less. Such ultra-thin coatings can be particularly useful for applications wherein a substantially thicker coating would otherwise obscure at least a part of the function of the device. These applications for “ultra thin” coatings are numerous and include, for example, coating surfaces that provide either small pore sizes or structural features of less than about one micron in size.
One general approach to providing an ultra-thin coating has been described in U.S. Pat. No. 6,689,473 (Guire et. al.) which describes forming an ultra-thin coating on a surface using amphiphilic-self assembling monolayer (SAM) molecules and latent reactive groups (such as photoreactive groups). The SAM molecules can be covalently coupled to a surface and/or coupled together to form a thin-coated layer on the surface of the article. These SAM-coated surfaces are useful for a number or purposes, including passivation against protein absorption and bacterial adherence, passivation against non-specific absorption on a biosensor, and preparation of an oligonucleotide array. Self-assembled monolayer (“SAM”) technology has been used to generate monomolecular films of biological and non-biological (e.g., synthetic polymeric) molecules on a variety of substrates. The formation of such monolayer systems is versatile and can provide a method for the in vitro development of bio-surfaces which are able to mimic naturally occurring molecular recognition processes. SAMs also permit reliable control over the packing density and the environment of an immobilized recognition center or multiple centers, at a substrate surface.
Despite some progress, advancement in this technological area is still needed to provide ultra-thin coatings having properties such as complete and uniform surface coverage, hydrophilic properties, minimal nonspecific attraction for biomolecules and cells, sufficient stability and durability, broad applicability to various material surfaces, and ease and reproducibility for forming the coating. Furthermore, the coating should be easily formed by conventional manufacturing processes. In some cases it would also be desirable to prepare coatings that are resistant to conventional sterilization techniques that are used to prepare medical articles for use. In addition, it is also desirable to utilize coating materials that are not costly or that are relatively straightforward to synthesize.
What is clearly needed are methods and reagents for providing improved surface coatings, including those having further improved combinations of the various desirable properties listed above.